We propose a study to examine strategies to deliver a promising preventive HIV vaccine candidate-employing a surrogate hepatitis B vaccine-to a cohort of high-risk young injection drug users (IDU) and young male IDU that have sex with men (MSM-IDU). We will screen 750 IDU aged 29 or less in San Francisco and over sample MSM-IDU, who have very high rates of HIV seroconversion. We expect that about 50% of those screened will meet eligibility criteria for prospective study and of those, that 80% will enroll. We will follow this cohort of 300 individuals for one year, administering a combined hepatitis A virus (HAV) inactivated and hepatitis B virus (HBV) recombinant vaccine (Twinrix() to study medical management and implementation issues, including: (1) adherence to multi-dose immunization schedules, (2) novel methods to minimize losses to follow-up, and (3) physiologic and behavioral factors that may alter vaccine effectiveness. The primary purpose of the study is to efficiently compare interventions to improve vaccine series adherence. In particular, we propose a randomized trial using a factorial design to compare the effects of clinical setting (syringe exchange program vs. immunization clinic) and outreach worker support (outreach vs. none) in enhancing adherence to a multiple dose immunization schedule. We have three secondary objectives. The first focuses on transience, one of the major causes of attrition in cohort studies of often-homeless IDU and other disenfranchised populations. For subjects who leave San Francisco during the study period, we will use novel technology to map their travel and achieve immunizations remotely. Secondly, we will compare vaccine effectiveness between HCV-infected and uninfected young IDU. We will measure protective antibody levels after immunizations. Finally, given the potential for reduced vaccine effectiveness in the setting of continued high-risk behavior, we will measure changes in behavior and vaccine attitudes. By testing strategies for delivering a multi-dose schedule of hepatitis vaccine and developing models for improving future HIV vaccine adherence and effectiveness, we can advance HIV vaccine development for young adult high-risk injection drug users.